Longitudinal Dynamics of Antimicrobial Resistance Gene Flux in ICU Patients Undergoing Broad-Spectrum Antibiotic Therapy at Tertiary Hospitals in South South Nigeria

The impact of broad-spectrum antibiotic therapy on the longitudinal trajectory of gut resistome dynamics in ICU patients represents a frontier research question with direct clinical implications for antimicrobial stewardship and infection control. Patient-level resistome dynamics under antibiotic pressure in Nigerian ICU settings have not been prospectively characterized. This longitudinal metagenomics study tracked gut resistome flux in 60 ICU patients at tertiary hospitals in Rivers State and Delta State, South South Nigeria, receiving broad-spectrum antibiotic therapy. Serial stool or rectal swab samples were collected at baseline (ICU admission), days 3, 7, 14, and at ICU discharge. Shotgun metagenomics was performed on all samples, with ARG profiling using CARD and microbial community analysis using MetaPhlAn3. Clinical outcomes including length of stay, secondary infection incidence, and 30-day mortality were recorded. Results showed that broad-spectrum carbapenem therapy within 48 hours produced the most dramatic resistome expansion, with blaNDM and blaOXA gene abundances increasing 12 to 25-fold by day 7. Microbiome diversity (Shannon index) declined by an average of 63 percent by day 3 and did not recover to baseline levels by discharge in 78 percent of patients. Resistome expansion magnitude at day 7 was a significant predictor of secondary MDR infection (HR: 3.8) and 30-day mortality (HR: 2.4). Resistome contraction following carbapenem de-escalation was observed in 55 percent of patients where stewardship-guided de-escalation was implemented. This study constitutes an original longitudinal resistome contribution and provides the first ICU-level AMR gut dynamics data from South South Nigeria. Keywords: ICU resistome, longitudinal metagenomics, antibiotic therapy, gut dysbiosis, South South Nigeria.